arsenic trioxide in treating men with germ cell cancer

Conditions: Extragonadal Germ Cell Tumor; Testicular Germ Cell Tumor

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. purpose: phase ii trial to study the effectiveness of arsenic trioxide in treating men who have germ cell cancer that has not responded to previous treatment.

objectives: * determine the response rate (confirmed complete and partial responses) in men with refractory testicular or extragonadal germ cell malignancies treated with arsenic trioxide. * determine the overall and progression-free survival of patients treated with this drug. * determine the qualitative and quantitative toxic effects of this drug in these patients. * assess the biomarker response rate in patients with elevated biomarkers treated with this drug. outline: this is a multicenter study. patients receive arsenic trioxide iv over 1-2 hours on days 1-5. courses repeat every 28 days for up to 3 years in the absence of disease progression or unacceptable toxicity. patients who achieve a confirmed complete or partial response receive up to 3 additional courses past response. patients are followed every 2 months for 3 years or until disease progression. projected accrual: a total of 20-40 patients will be accrued for this study within 10-40 months.

Eligibility criteria:
disease characteristics: * histologically confirmed testicular or extragonadal germ cell cancer * refractory disease, defined by at least 1 of the following criteria: * disease progression during or within 4 weeks of cisplatin-containing regimen * progression is defined as the appearance of new or progression of known locally advanced or metastatic disease or a rise in tumor markers (beta-human chorionic gonadotropin (beta-hcg) or alpha fetoprotein (afp)) by at least 50% relative to the nadir * when the only evidence of germ cell progression or recurrence before study entry is the appearance of a new lesion in the absence of tumor marker elevation, a biopsy is required to confirm the diagnosis * disease recurrence after at least 2 chemotherapy regimens, one of which includes high-dose therapy (chemotherapy with stem cell support) * disease recurrence after at least 2 chemotherapy regimens and not eligible for high-dose therapy * at least 1 of the following: * unidimensionally measurable disease * soft tissue, irradiated within the past 2 months, is not considered measurable * elevated beta-hcg (more than 20 miu/ml) * afp greater than 2 times upper limit of normal patient characteristics: age: * 16 and over sex: * male performance status: * zubrod 0-2 life expectancy: * not specified hematopoietic: * absolute granulocyte count at least 1,500/mm\^3 * platelet count at least 100,000/mm\^3 * wbc at least 3,000/mm\^3 hepatic: * bilirubin less than 2.5 times upper limit of normal (uln) * sgot less than 5 times uln * alkaline phosphatase less than 5 times uln renal: * creatinine no greater than 2.5 times uln or * creatinine clearance at least 40 ml/min * potassium normal * magnesium normal * no renal dialysis cardiovascular: * no prior torsades de pointes-type ventricular arrhythmia * no prolonged qt interval (greater than 450 msec) on ecg in presence of normal potassium and magnesium other: * fertile patients must use effective contraception * no active serious infection not controlled by antibiotics * no known hypersensitivity to arsenic * no other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer or stage i or ii disease in complete remission prior concurrent therapy: biologic therapy: * see disease characteristics chemotherapy: * see disease characteristics * more than 28 days since prior cytotoxic agents endocrine therapy: * not specified radiotherapy: * see disease characteristics * at least 28 days since prior radiotherapy and recovered surgery: * not specified other: * more than 28 days since prior experimental agents * no concurrent or planned drugs known to prolong the qt interval

Keywords: recurrent malignant testicular germ cell tumor extragonadal germ cell tumor